Production of axerophthyl phosphonium salts



United States Patent C) ce 3,294,844

Patented Dec. 27, 1966 1 2 3 294 844 depending on the type of solvent and of vitamin A ester. The reaction period depends on a number of factors, inv FQQ E cluding the reaction temperature. For example some Wilhelm Samecki, Axel Nuenenbach, and Wemer Reie, days are required for the reaction between vitamin A Ludwigshafen (Rhine), Germany, assignors to Badische 5 acetate, triphenylphosphine and sulfuric acid at t p Anilin- & Soda-Fabrik Aktiengesellschaft, Ludwigshatures of about l0 C., but only a few minutes at fen (Rhine), Germany +80 C.

N0 P P Filed M y 1963, 231,790 The reaction according to this invention, in which equi- Clalms P apphcatlglzggmanya May 19621 molar amounts of the reactants react with each other, proceeds, for example in the case of the last-mentioned 7 Claims (CL 260-6065) 10 reaction above, according to the following equation:

H 0 CH CH3 CH3 0 This invention relates to a new process for the pro- The process according to this invention represents a duction of axerophthyl phosphonium salts in which the 25 considerable advance in the art because it is now posaxerophthyl radical (I): sible to prepare in pure form the quaternary axerophthyl H3O CH3 phosphonium salts which are valuable intermediates for CH CH3 syntheses of carotene and other carotenoids, direct from esters of axerophthol (vitamin A alcohol). This is of great advantage because in commercial processes axero- OHS phthol is usually obtained in the form of its esters which (I) are more readily accessible and more stable than is one f the fourligands of phosphorus the alcohol. Moreover vitamin A is often present in Axerophthyl phosphonium Salts are Valuable intermedinature 1n the ester form. Since in all industrial vitamin ates for syntheses in the vitamin A series. A Syntheses, the e r 5 pr p as the end P It is the object of this invention to prepare these comwz'iste fvhlch Contam the ester are always pounds in a particularly expedient and the most economitamed and it is troublesome to isolate the ester from Cal way possible them. Such waste liquors may now be worked up di- We have found that quaternary axerophthyl phosmet to axerophthyl phosphonium Saltsphonium salts are obtained in excellent yields by quater- 40 The fact P axerfphthol Sters can be converted nizing tertiary phosphines with esters of axerophthyl feet and Wlthout dlfiiculty Into the quaternary P (vitamin A alcohol) Le by reacting esters of aXem phonium salts is astonishing because according to US. phthol (vitamin A alcohol) with tertiary phosphines and patent specification No. 2,905,717, which describes the acids or with the hydrosalts of tertiary phosphines. PYOdQCHOH of quatfimmy phosphonium Salts from P Not only are the esters of all-trans-vitamin A alcohol Phomum hydl'ohalldes aI 1d a1c0h01s ester groups do not suitable for the process according to this invention but take Y Pan l reactlonalso esters of cis-vitarnin A alcohol, particularly esters The f i 15 further illustrated by the following of low molecular weight fatty acids, such as acetic acid exgmpks m Whlch, P Otherwise Stated Parts by and propionic acid. weight. Parts by welght bear the same relation to parts Tertiary phosphines having aromatic radicals, for exby Volume as the kflogmm to the liter amplzle giaryl lliphosphlines, suclh as tri -p-tolylphosph ine, tri- Example 1 g g i me an pamcu at y tnphenylphosphme are A mixture of 36 parts of triphenyl phosphonium hydro- Suitable acids are inorganic and organic acids which gen Sulfate 339mg of afll'trans'lmarpin A acetate and will form salts with the tertiary phosphines, as for ex- 250 parts by Volume of methanol 18 Stine? at room temample organic sulfonic acids, such as benzenesulfonic 50 perature for several hours. The solvent is then distilled acids and toluenesulfonic acids, and particularly sulfuric Off f subatm'osphn? priassure t temprature acid Suitable hydrosalts of the tertiary phosphines are of 40 C., and the (llSlllllfitlOn residue dlSSO'lVCd in 100 the tertiary phosphonium salts of the said acids, for exparts volume of acetorllmle an.d.St1rre.d for three hours ample triphenyl phosphonium Sulfate. at 10 C. The crystalline precip tate is filtered off and The reaction is advantageously carried out in solvents, dned' 54 Parts, of aemphthy1npheqy1 phosphonium for example in benzene, toluene, diethyl ether, tetrahydrohydrogen sulfate Obtamed (meltmg Point: 1940 furan, alcohols and acid derivatives, such as acetonitrile 1 phosphorus content: 48%; E 1 339 mini and acetic esters. Polar solvents, such as alcohols and mlcrongzmj) acetonitrile, are preferred. When the solvent is correct- Example 2 1y chosen, the quaternary phosphonium S c ystallizes 36 parts of an industrial waste oil containing up to out in many cases and can then be filtered ofi direct. about 30% of cisand trans-vitamin A acetate is stirred The reaction temperature may vary within wide limits, ith 27 parts of triphenyl phosphonium hydrogen sulfate for example from 20 to +120 C. In the upward in 250 parts by volume of ethyl acetate for fifteen hours direction it is mainly limited by the temperature at which at room temperature and then for another three hours in the vitamin A ester begins to decompose. It is advanan ice-bath. The precipitate is filtered off, washed with tageous to work at temperatures between 0 and C., cold ethyl acetate and dried.

Example 3 A mixture of 26.5 parts of triphenylphosphine, 21 parts of 90% p-toluenesulfonic acid, 33 parts of vitamin A acetate and 100 parts by volume of methanol is stirred for fifteen hours at room temperature and another two hours at 40 C. The solvent is then evaporated in a water jet vacuum at a bath temperature at 40 C. The residue is digested four times, each time in 100 parts by volume of absolute ether. decanted off, the residual viscous oil is freed from other residues in vacuo'. 63 parts of axerophthyltriphenyl phosphonium p-toluenesulfonate is obtained (E (1%, 1 cm., 337 millimicrons)=640).

Example 4 is then cooled to 5 to C. and stirred for another 3 seven hours. The crystal mash is filtered off and dried.

34 parts of crude axeropht-hyltriphenyl phosphom'um hy drogen sulfate is obtained (melting point 177 C.; E (1%, 1 cm., 339 -rni llimicrons)=620).

Example 5 A mixture of 36 parts of triphenyl phosphonium hydro- 'gen sulfate, 53 parts of a 94% concentrate of vitamin A palrnitate and 150 parts of methanol is stirred for two hours at 40 C. After a :few hours more, the solvent is evaporated in a water jet vacuum at a bath temperature of 40 C. The residue is digested twice, each time with 100 parts by volume of absolute ether.

The ether is decanted off, 150 parts by volume of acetonitrile added to the residue and the whole stirred for one hour at 0 C. The precipitate is filtered oif and dried. 45 parts of axerophthyltriphenyl phosphonium hydrogen sulfate which still contains some palmitic acid is obtained (melting point 169 C.; E (1 cm., 1%, 338 millimicrons)=654).

After the ether has been 4 Example 6 32.8 parts of crystalline vitamin A acetate is added at room temperature to a mixture of 26.5 parts of triphenylphosphine and 18.4 parts of a 47.8% ethereal fluoboric acid in 100 parts by volume of ethyl acetate.

After the whole has :been stirred for twenty-four hours, the .axerophthyltrip-henyl phosphoniurn fluoborate is precipitated with n-octane. 68 parts of the said salt is obtained (E (1%, 1 cm, 338 millirnicrons) :496).

We claim:

1. A process for the production of quaternary axerophthyl phosphonium salts which comprises: reacting an ester of axerophtho-l with a member selected from the group consisting of a tertiary phosphine and a hydrosalt of a tertiary phosphine, with the proviso that where a tertiary p-hosphine is used as the reactant, an acid which will form with the tertiary phosphine a hydrosalt is present in the reaction mixture.

2. A process as in claim 1 wherein the tertiary phosphine is tria=ryl phosphine.

3. A process as in claim 1 wherein the reaction is carried out at a temperature between 0 and C.

4. A process as in claim 1 wherein the reaction is 'carried out in the presence of an inert organic solvent.

5. A process as in claim 1 wherein an ester of cisaxerophthol is used as an initial reactant.

6. A process as in claim 1 wherein a waste liquor containing an ester of axerop-hthol, which liquor has been obtained in the production and purification of said ester, is used as an initial reactant.

7. A process as in claim 1 wherein an acid selected from-the group consisting of sulfuric acid, fluoboric acid, benzene sulfonic acid, and toluene snlfonic acid is used as the acid which will form hydrosa-lts with said tertiary phosphine.

No references cited.

TOBIAS E. LEVOW, Primary Examiner.

W. F. W. BELLAMY, Assistant Examiner.

UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION Patent No. 3,294,844 December 27, 1966 Wilhelm Sarnecki et a1 It is hereby certified that error appears in the above numbered patent requiring correction and that the said Letters Patent should read as corrected below.

In the heading to the printed specification, line 4, for "Werner Reie" read Werner Reif Signed and sealed this 5th day of November 1968.

(SEAL) Attest:

Edward M. Fletcher, Jr. EDWARD J. BRENNER Attesting Officer Commissioner of Patents Notice of Adverse Decision in Interference In Interference No. 96,313 involvin Patent No. 3,294,844, W. Salnecki, A. Nuerrenbach and \V. Reif, PROl UCTlON OF AXEROPHTHYL PHOSPHONIUM SALTS, final judgment adverse to the patentees was rendered Sept. 22, 1969, as to claims 1, 2, 3, 4, and 7.

[Ofiicial Gazette March 17, 1970.] 

1. A PROCESS FOR THE PRODUCTION OF QUATERNARY AXEROPHTHYL PHOSPHONIUM SALTS WHICH COMPRISES: REACTING AN ESTER OF AXEROPHTHOL WITH A MEMBER SELECTED FROM THE GROUP CONSISTING OF A TERTIARY PHOSPHINE AND A HYDROSALT OF A TERTIARY PHOSPHINE, WITH THE PROVISO THAT WHERE A TERTIARY PHOSPHINE IS USED AS THE REACTANT, AN ACID WHICH WILL FORM WITH THE TERTIARY PHOSPHINE A HYDROSALT IS PRESENT IN THE REACTION MIXTURE. 